To optimize the fermentation process of mulberry wine, fermenting temperature, cane sugar adding level, and inoculating quantity were used as dependent variables, and residual sugar content, total acids, total flavonoids, ethanol content, and sensory comprehensive score were used as independent variables. On the basis of single-factor experiments, 3-factor and 5-level central composite design was adopted, then validation test was conducted. The optimal fermentation parameters were summed up as follows through design expert 7 processing: fermenting temperature was at 15.3 ℃, inoculating quantity was 8.00 g/L, and cane sugar adding level was 12.80 g/100 g. The predicted values of mulberry wine were as follows: total residual sugar content was 3.18 g/L, total acids content was 6.82 g/L, total flavonoids content was 410.49 mg/L, ethanol content was 14.12 %vol, and comprehensive sensory score was 81.91. The validation test demonstrated that, total residual sugar content was 3.27 g/L, total acids content was 6.61 g/L, total flavonoids content was 405.21 mg/L, ethanol content was 14.21 %vol, and comprehensive sensory score was 82.33. The bias ratio of predicted values and real values were -2.8 %, 3.1 %, 1.3 %, -0.6 %, and -0.5 % respectively. On the basis of the optimized fermentation parameters, 3 wine samples were prepared and their predicted values and real values were very close, which proved the good predictability of the established regression equation.